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Relationship between FH tumor-suppressor gene and aerobic glycolysis (Warburg effect)

Research Project

Project/Area Number 26462426
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionDokkyo Medical University

Principal Investigator

Kamai Takao  獨協医科大学, 医学部, 教授 (80316562)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords腎細胞癌 / HLRCC / Akt / Nrf2 / aerobic glycolysis / FH遺伝子 / 腎癌
Outline of Final Research Achievements

The main findings of the present study were as follows: 1) A higher standard glucose uptake value (SUVmax) on 18F-FDG-PET was correlated with higher expression of phosphorylated Akt(Ser-473) in the primary tumor. A higher SUVmax and increased expression of phosphorylated Akt(Ser-473) was associated with a higher pT stage,and metastasis, as well as shorter overall survival in RCC patients. 2) Targeted next-generation sequencing revealed that fumarate hydratase (fumarase, FH) mutation and loss of the second allele were completely identical between blood and tumor samples in Hereditary Leiomyomatosis and Renal Cell Cancer(HLRCC)cancer patients. Furthermore, surgically resected samples showed high expression of phosphorylated Akt(Ser-473) as well as nuclear factor E2-related factor 2 (Nrf2), suggesting that FH mutation plays a direct role in a metabolic shift to aerobic glycolysis), and increased an anti-oxidant response phenotype in HLRCC-associated kidney cancer.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (2 results)

All 2016

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results)

  • [Journal Article] Radical nephrectomy and regional lymph node dissection for locally advanced type 2 papillary renal cell carcinoma in an at-risk individual from a family with hereditary leiomyomatosis and renal cell cancer: a case report2016

    • Author(s)
      Takao Kamai, Hideyuki Abe, Kyoko Arai, Satoshi Murakami, Setsu Sakamoto, Yasushi Kaji
    • Journal Title

      BMC Cancer

      Volume: 16 Issue: 1 Pages: 232-232

    • DOI

      10.1186/s12885-016-2272-7

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Higher preoperative serum levels of PD-L1 and B7-H4 are associated with invasive and metastatic potential and predictable for poor response to VEGF-targeted therapy and unfavorable prognosis of renal cell carcinoma2016

    • Author(s)
      Takehiko Fukuda, Takao Kamai, Akinori Masuda, Akinori Nukui, Hideyuki Abe, Kyoko Arai, Ken-Ichiro Yoshida
    • Journal Title

      Cancer Medicine

      Volume: 5(8) Issue: 8 Pages: 1810-1820

    • DOI

      10.1002/cam4.754

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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